Advisable including glucosaminylmuramyldipeptide in Helicobacter pylori therapy: experience of ten-year investigation

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Abstract

Helicobacter pylori infection is a common bacterial infection in humans and is associated with peptic ulcer disease and chronic gastritis. The presence of natural resistance to some antibiotics in bacteria, as well as the appearance of primary and secondary resistance to antibacterial agents, complicates treatment and determines the search for new methods of therapy. The aim of this study was to evaluate the efficacy and safety of 10-year complex treatment of patients with duodenal ulcer associated with H.pylori , 136 patients (96 men, 40 women; mean age 45.8 ± 14.8 years; 18-65 years). H.pylori was determined morphologically and by rapid urease test one day before the start of therapy, after 1, 6, 12 months, 2 years, 5 and 10 years. Patients of the first group received basic therapy: omeprazole 0.02 g 2 times a day, clarithromycin 0.5 g 2 times a day, amoxicillin 1 g 2 times a day, for 10 days (OCA group 1; n = 98). Patients of the second group, in addition to the basic therapy, took 1 mg per day drug Liсopid (group 2 OСAL; n = 38). At the 1st stage of the clinical study, 130 patients completed eradication therapy. Tracking completeness was 96 %. The frequency of H.pylori eradication after per protocol treatment: OCA - 83 % (95 % CI: 75 %-91 %), OCAL - 97 % (95 % confidence interval (CI): 92 %-100 %). The incidence of adverse reactions after treatment (per protocol): OCA - 26 % (95 % CI: 17-35 %; nausea; n = 24), discontinued treatment - 5 % (95 % CI: 0.8 %-10 %; diarrhea; n = 5); OCAL - 3 % (95 % CI: 0.01 %-8 %; nausea; n = 1), all were treated. Taking the drug Liсopid 1 mg (glucosaminyl muramyl dipeptide, JSC Peptek, Russia) as part of complex therapy contributed to the elimination of H.pylori and the absence of relapses for 2 years. Observation of patients in the next 5 and 10 years also showed the advantage of including the immunomodulator in therapy: a significant 15 % decrease in H.pylori reinfection (P <0.05), a 23 % decrease in the frequency of gastrointestinal adverse reactions (P<0.01), compared with a 10-day standard triple regimen without immunomodulatory therapy with glucosaminylmuramyl dipeptide. When using several antibiotics in H.pylori eradication therapy, not only pathogenic, but also commensal microorganisms are destroyed, the waste products of which are vital and maintain immune homeostasis, including through the NOD2 receptors of innate immunity. The effectiveness of the complex therapy of H.pylori infection can be explained by the fact that the drug Liсopid compensates for the signal for innate immunity receptors that is missing due to the absence of commensals, providing an adequate immune response and preventing chronicity and recurrence of infection.

About the authors

M. R Konorev

Vitebsk State Medical University

Author for correspondence.
Email: svgur@mail.ru
Vitebsk, Belarus

S. V Guryanova

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS; Peoples’ Friendship University of Russia (RUDN University)

Email: svgur@mail.ru
Moscow, Russian Federation

E. N Tyshevich

Vitebsk State Medical University

Email: svgur@mail.ru
Vitebsk, Belarus

R. A Pavlyukov

Vitebsk State Medical University

Email: svgur@mail.ru
Vitebsk, Belarus

O. Yu Borisova

Moscow Research Institute of Epidemiology and Microbiology named after G.N. Gabrichevsky

Email: svgur@mail.ru
Moscow, Russian Federation

References

  1. Malfertheiner P., Megraud F., O’Morain C.A., et al. Management of Helicobacter pylori infection - the Maastricht-IV / Florence Consensus Report. Gut. 2012; 61: 646-664. doi: 10.1136/ gutjnl-2012-302084
  2. Malfertheiner P., Megraud F., O’Morain C.A., et al. Management of Helicobacter pylori infection - the Maastricht V / Florence Consensus Report. Gut. 2017; 66: 6-30. doi: 10.1136/gutjnl-2016-312288
  3. Hunt R., Xiao S.D., Megraud F., et al. Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J. Gastrointestin. Liver Dis. 2011; 20(3): 299-304. doi: 10.1097/MCG.0b013e31820fb8f6
  4. Marshall B.J. Warren J.R. Unidentified curved bacilli on gastric ileum in active chronic gastritis. Lancet. 1983; 1: 1273-1275.
  5. Sugano K., Tack J., Kuiperset E.J. et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015; 64(9): 1353 doi: 10.1136/gutjnl-2015-309252
  6. Hopkins R.J. Current FDA-approved treatments for Helicobacter pylori and the FDA approval process. Gastroenterology. 1997; 113(6, Suppl): S126-30.
  7. Ivashkin V.T., Maev I.V., Lapina T.L. et al. Clinical guidelines of the Russian Gastroenterological Association for the diagnosis and treatment of Helicobacter pylori infection in adults. Grew up. Gastroenterol. hepatol. coloproctol. 2018; 28 (1): 55-70.
  8. Minushkin O.N., Osokina A.P., Shuleshova A.G. and others. Long-term results of successful eradication of Nonlicobacter pylori in patients with duodenal ulcer. Kremlin medicine. Clinical Bulletin. 2012; 1: 123-126. (in Russian)
  9. Burakov I.I. Results of long-term observation of patients with peptic ulcer disease associated with Helicobacter pylori after eradication of the microorganism. Experiment. and a wedge. Gastroenterol. 2002; 3: 45-48. (in Russian)
  10. Hu Y., Wan J.-H., Li X.-Y. et al. Systematic review with metaanalysis: the global recurrence rate of Helicobacter pylori. Aliment. Pharmacol. Ther. 2017; 46: 773-779. doi: 10.1111/apt.14319
  11. Lionetti E., Indrio F., Pavone L., et al. Role of probiotics in pediatric patients with Helicobacter pylori infection: a comprehensive review of the literature. Helicobacter. 2010; 15(2): 79-87. doi: 10.1111/j.1523-5378.2009.00743.x
  12. O’Connor А. et al. Treatment of Helicobacter pylori infection 2019. Helicobacter. 2019; 24(Suppl.1): e12640. doi: 10.1111/ hel.12640
  13. Gill H.H., Prasad J. Probiotics, immunomodulation and health benefits. Adv. Exp. Med. Biol. 2008; 606: 423-454.
  14. Pinegin B.V., Andronova T.M. Some theoretical and practical issues of the clinical use of the immunomodulator lycopid. Immunologiya.1998; 4: 60-63. (in Russian)
  15. Guryanova S.V., Khaitov R.M. Glucosaminylmuramyldipeptide - GMDP: effect on mucosal immunity (on the issue of immunotherapy and immunoprophylaxis). Immunologiya. 2020; 41 (2): 174-83. doi: 10.33029/0206-4952-2020-41-2-174-183 (in Russian)
  16. Meshcheryakova E., Makarov E., Philpott D., Andronova T., Ivanov V. Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipophilic derivatives of N-acetylglucosaminy N-acetylmuramyl peptides. Vaccine. 2007; 25: 4515-20.
  17. Laman A.G., Lathe R., Shepelyakovskaya A.O., Gartseva A., Brovko F.A., Guryanova S., Alekseeva L., Meshcheryakova E.A., Ivanov V.T. Muramyl peptides activate innate immunity conjointly via YB1 and NOD2. Innate Immunity. 2016. Т. 22. № 8. С. 666-673. doi: 10.1177/1753425916668982
  18. Krasheninnikov A.E., Matveev A.V., Andronova T.M., Guryanova S.V., Shilova N.V., Kozlov I.G. Safety of using the preparation “LICOPID®” in opinion of experts in various specialities. Perm Medical Journal. 2019.Vol. 36. No. 2. P. 81-92. (in Russian) doi: 10.17816/pmj36281-92
  19. Guryanova S.V. Antibiotic resistance: ligands of innate immunity take the challenge. Allergy. 2018. Т. 73. № S105. С. 581.
  20. Abramashvili Yu. G., Kolesnikova N.V., Borisova O. Yu., Guryanova S.V. Low molecular weight bioregulator of bacterial origin in condylomatosis therapy optimization. RUDN Journal of Medicine. 2020 Mar; 24 (2): 163-167. doi: 10.22363/2313- 0245-2020-24-2-163-167
  21. Kozlov I.G., Guryanova S.V., Kolesnikova N.V., Andronova T.M. Muramyl peptides and other agonists of innate immunity receptors in the treatment of allergic diseases. Rossiyskiy allergologicheskiy zhurnal. 2015; 5: 59-67. (in Russian)
  22. Kozlov I.G., Kolesnikova N.V., Voronina E.V., Guryanova S.V., Andronova T.M. Glucosaminylmuramyl dipeptide and other innate immunity receptor agonists in the pathogenetic treatment of allergic diseases. Allergologiya and immunologiya. 2013; 14 (4): 281-7. (in Russian)
  23. Guryanova S., Udzhukhu V., Kubylinsky A. Pathogenetic therapy of psoriasis by muramyl peptide. Frontiers in Immunology. 2019. Т. 10. № JUN. С. 1275. doi: 10.3389/fimmu.2019.01275
  24. Manapova E.R., Fazylov V. Kh., Guryanova S.V. cytopenia and their correction in antiviral therapy of chronic hepatitis C in patients with genotype 1. Problems of Virology. 2017; 62(4):174-8. doi: 10.18821/0507-4088-2017-62-4-174-178
  25. Guryanova S.V., Borisova O.Yu., Kolesnikova N.V., Lezhava N.L., Kozlov I.G., Gudima G.O. The effect of muramyl peptide on the microbial composition of the microfl ora of the oral cavity. Immunologiya. 2019; 40 (6): 34-40. doi: 10.24411/0206-4952- 2019-16005. (in Russian)
  26. Konorev M.R. The influence of lycopid on the persistence of Helicobacter pylori in the gastric mucosa of patients with chronic gastritis. Immunopathology, allergology, infectology. 2004; 2: 33-34. (in Russian)
  27. Konorev M.R. Use of the immunopotentiator N-acetyl-glucosamine-N-acetyl-muramyl dipeptide during triple anti-Helicobacter pylori therapy. Ter Arkh. 2012; 84(12): 65-69. (in Russian)
  28. Tytgat G.N. The Sydney system, endoscopic division: endoscopic appearance in gastritis. J. Gastroenterol. Hepatol. 1991; 6(3): 223-234.
  29. Aruin L.I., Grigoriev P.Ya., Isakov V.A., Yakovenko E.P. Chronic gastritis. Amsterdam, 1993: 3-362.
  30. Konorev M.R., Litvyakov A.M., Krylov Yu.V., Matveenko M.E. Chronic duodenitis. Minsk: Doctor Design LLC, 2003.
  31. Price A.B. The Sydney system: Histological division. J. Gastroenterol. Hepatol. 1991; 6(3): 209-222.
  32. Dixon M. et al. Classification and grading of gastritis. Am. J. Surg. Pathol. 1996; 20: 1161-1181.
  33. Kido M., Tanaka J., Aoki N., et al. Helicobacter pylori promotes the production of thymic stromal lymphopoietin by gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2 responses. Infect. Immun. 2010; 78(1): 108-114.
  34. Chang C., Pan S., Lien Gi., et al. Investigation of the extent of gastric metaplasia in the duodenal bulb by using methylene blue staining. J.Gastroenterol.Hepatol. 2001; 16(7): 729-739.
  35. Aruin L.I., Kapuller L.L., Isakov V.A. Morphological diagnosis of diseases of the stomach and intestines. M.: Triada-X, 1998: 13-496.
  36. Konorev M.R., Matveenko M.E., Krylov A.Yu. et al. Rapid urease test Helpil for the diagnosis of Helicobacter pylori infection. S.Pb., 2013: 1-38. (in Russian)
  37. Betty R. Essential medical statistics. 2nd ed. Kirkwood and Jonathan A. C. Sterne: Blackwell Science Ltd., 2003: 414-425.
  38. Pimanov S.I., Makarenko E.V., Voropaeva A.V. et al. Prerequisites for Empirical Eradication Therapy in Patients With Duodenal Ulcer: Study in Belarus. Helicobacter. 2003; 8: 475.
  39. Konorev M.R., Litvyakov A.M., Krylov Yu.V. et al. Chronic duodenitis associated with Helicobacter pylori. Clinical medicine. 1999; 77 (11): 49-52. (in Russian)
  40. Konorev MR., Andronova TM., Matveenko ME. Use of probiotics and probiotic-based immunomodulators as adjuvant therapy for Helicobacter pylori eradication. Ter Arkh 2016; 88(12): 140148.) (in Russian)
  41. Nikitushkin VD, Demina GR, Shleeva MO, Guryanova SV, Ruggiero A, Berisio R, Kaprelyants AS. A product of RpfB and RipA joint enzymatic action promotes the resuscitation of dormant mycobacteria. FEBS J. 2015 Jul;282(13):2500-11. doi: 10.1111/ febs.13292.
  42. Rosenstiel P., Hellmig S., Hampe J., et al. Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection. Cell. Microbiol. 2006; 8(7): 1188-1198.
  43. Claes A.K., Zhou J.Y., Philpott D.J. NOD-Like Receptors: Guardians of Intestinal Mucosal Barriers. Physiology (Bethesda). 2015; 30(3): 241-250. doi: 10.1152/physiol.00025.2014
  44. Fan X.G., Yakoob J., Fan X.J., Keling P.W. Enchanced T-helper 2 Lymphocyte responses: immune mechanism of Helicobacter pylori infection. Ir. J. Med.Sci.1996;165(1):37-39.
  45. Beigier-Bompadre M., Moos V., Belogolova E., et al. Modulation of the CD4+ T-cell response by Helicobacter pylori depends on known virulence factors and bacterial cholesterol and cholesterol α-glucoside content. J. Infect. Dis. 2011; 204(9): 1339-1348.
  46. Konorev M.R., Konevalova N.Yu. Modern concepts of the immune system associated with the intestinal mucosa. Immunopathology, allergology, infectology. 2010; 2: 40-46.
  47. Larussa T., Leone I., Suraci E., et al. Helicobacter pylori and T Helper Cells: Mechanisms of Immune Escape and Tolerance. J. Immunol. Res. 2015; 2015: 981328.
  48. Guryanova S.V., Kozlov I.G., Meshcheryakova E.A., Alekseeva L.G., Andronova T.M. Glucosaminylmuramyl dipeptide normalizes the Th1 / Th2 balance in atopic bronchial asthma. Immunologiya. 2009; 5: 305-8. (in Russian)
  49. Tong J.L., Ran Z.H., Shen J., et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment. Pharmacol. Ther. 2007; 25(2): 155-168. doi: 10.1111/j.13652036.2006.03179.x.
  50. Zou J., Dong J., Yu X. Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple first-line therapy for Helicobacter pylori eradication. Helicobacter. 2009; 14(5): 97107. doi: 10.1111/j.1523-5378.2009.00716.x.
  51. Sachdeva A., Nagpal J. Effect of fermented milk-based probiotic preparations on Helicobacter pylori eradication: a systematic review and meta-analysis of randomized-controlled trials. Eur. J. Gastroenterol. Hepatol. 2009; 21(1): 45-53. doi: 10.1097/ MEG.0b013e32830d0eff
  52. Szajewska H., Horvath A., Piwowarczyk A. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment. Pharmacol. Ther. 2010; 32(9): 1069-1079. doi: 10.1111/j.1365-2036.2010.04457.x
  53. Wang Z.H., Gao Q.Y., Fang J.Y. Meta-analysis of the efficacy and safety of Lactobacillus-containing and Bifidobacterium-containing probiotic compound preparation in Helicobacter pylori eradication therapy. J. Clin. Gastroenterol. 2013; 47(1): 25-32. doi: 10.1097/MCG.0b013e318266f6cf
  54. Zheng X., Lyu L., Mei Z. Lactobacillus-containing probiotic supplementation increases Helicobacter pylori eradication rate: evidence from a meta-analysis. Rev. Esp. Enferm. Dig. 2013; 105(8): 445-453. doi: 10.4321/S1130-01082013000800002.
  55. Li S., Huang X.L., Sui J.Z. et al. Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children. Eur. J. Pediatr. 2014; 173(2): 153-161. doi: 10.1007/s00431-013-2220-3
  56. Dang Y., Reinhardt J.D., Zhou X., Zhang G. The Effect of Probiotics Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Eradication Therapy: A Meta-Analysis. PLoS One. 2014; 9(11): e111030. doi: 10.1371/journal.pone.0111030
  57. Zhu R., Chen K., Zheng Y.-Y. et al. Meta-analysis of the efficacy of probiotics in Helicobacter pylori eradication therapy. World J. Gastroenterol. 2014; 20: 18013-18021. doi: 10.3748/wjg.v20. i47.18013
  58. Zhifa L.V., Wang B., Zhou X., et al. Efficacy and safety of probiotics as adjuvant agents for Helicobacter pylori infection: A meta-analysis. Exp. Ther. Med. 2015; 9(3): 707-716.
  59. Zhang M.M., Qian W., Qin Y.Y. et al. Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J. Gastroenterol. 2015; 21(14): 4345-4357. doi: 10.3748/ wjg.v21.i14.4345
  60. Lü M., Yu S., Deng J. et al. Efficacy of Probiotic Supplementation Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials. PLoS One. 2016; 11(10): e0163743. doi: 10.1371/journal.pone.0163743
  61. Lau C.S., Ward A., Chamberlain R.S. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis. Infect. Drug Resist. 2016; 9: 275-289. doi: 10.2147/IDR.S117886
  62. Shi X. et al. Efficacy and safety of probiotics in eradicating Helicobacter pylori. A network meta-analysis. Medicine (Baltimore). 2019; 98(15): e15180. doi: 10.1097/ MD.0000000000015180
  63. Losurdo G., Cubisino R., Barone M. et al. Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis. World J. Gastroenterol. 2018; 24(1): 139149. doi: 10.3748/wjg.v24.i1.139.
  64. Bogdanov I.G., Dalev P.G., Gurevich A.I. et al. Antitumour glycopeptides from Lactobacillus bulgaricus. FEBS Lett. 1975;57: 259-261.
  65. Cameron E.A.B., Bell G.D., Baldwin L., et al. Long-Term Study of Re-Infection Following Successful Eradication of Helicobacter pylori Infection. Alimentary Pharmacology & Therapeutics. 2006; 23(9): 1355-1358.

Copyright (c) 2020 Konorev M.R., Guryanova S.V., Tyshevich E.N., Pavlyukov R.A., Borisova O.Y.

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